DESCRIPTION: (From the applicant's abstract) "Prostate cancer is a devastating condition with enormous human and economic costs. Nearly 200,000 new cases will be diagnosed this year. Early detection of the disease relies on serum immunoassays for prostate specific antigen (PSA). However, there are two distinct forms of PSA that can be detected in serum which compromises the overall utility of the currently used immunoassays. Recent discoveries have indicated that reagents capable of quantifying these two species separately would greatly improve the accuracy and utility of early-detection procedures. The two major goals of this proposal are 1) to map the linear and non-linear epitopes on PSA and 2) define novel polypeptides which are capable of specifically binding to prostate-specific antigen (PSA), particularly ones capable of binding to the PSA-alpha-1-antichymotrypsin (ACT) complex. In the initial part of the proposed research, the regions of PSA most promising as targets for the diagnostic agents will be identified by epitope mapping using a panel of 30 monoclonal antibodies. In the second part, polypeptide libraries will then be screened for molecules which bind strongly and specifically to the two forms of PSA by means of a technology called "polysome screening." Suitable polypeptides identified in the "polysome screen" will be tested for their utility in clinical assays. Identification of these reagents and the development of improved assays for PSA is predicted to enhance the accuracy and decrease the costs for early detection of prostate cancer."